Human Papillomaviruses Types 16 and 18 
pression and replication. We have identified 
HPV- 1 8 enhancer sequences that are responsible 
for expression in maturing keratinocytes. The 
function of one of these sequences depends on 
the action of a cellular gene found only in epithe- 
lial cells, the keratinocyte-stimulating factor 
(KRF- 1 ) . We hope to understand the tissue spec- 
trum of expression of papillomaviruses by study- 
ing the epithelial-specific mechanisms for regula- 
tion of transcription. 
In collaboration M^ith Robert Hammer (HHMI, 
University of Texas Southwestern Medical Center 
at Dallas), we have developed an animal model 
for papillomavirus-induced disease. Transgenic 
mice have been constructed that express only E6- 
E7 genes of HPV- 18. These mice develop tumors 
of the urogenital tract : males develop seminal ves- 
icle tumors; females develop what appear to be 
tumors of the cervix. This demonstrates that HPVs 
are capable of inducing urogenital tumors in ani- 
mals. This model may thus be useful in the study 
of virally induced neoplasias. 
The study of HPV will provide information on 
mechanisms of transformation and tumor progres- 
sion, as well as tissue-specific expression and 
viral replication. 
In situ hybridization of raft culture of a cell line derived from a low-grade cervical neoplasm and 
containing episomal copies of HPV-31b. The dark spots indicate amplification of HPV viral ge- 
nomes in highly differentiated koilocyte-like cells, similar to the differentiation- dependent ampli- 
fication of HPV DNA that occurs in vivo. 
Prom Bedell, M.A., Hudson, f.B., Golub, T.R., Turyk, M.E., Hosken, M., Wilbanks, G.D., and 
Laimins, L.A. 1991. J Virol 65:2254-2260. 
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